FDA Approves Brigatinib as Frontline Treatment of ALK-Positive Metastatic NSCLC

The FDA has granted approval to brigatinib for the frontline treatment of patients with ALK-positive metastatic non–small cell lung cancer, as detected by an FDA-approved test.

The FDA has granted approval to brigatinib (Alunbrig) for the frontline treatment of patients with ALK-positive metastatic non–small cell lung cancer (NSCLC), as detected by an FDA-approved test.

This approval was based on findings from the phase 3 ALTA-1L clinical trial, which compared the efficacy and safety of brigatinib versus crizotinib (Xalkori) in patients with ALK-positive locally advanced or metastatic NSCLC who had not received prior ALK inhibitor treatment. Brigatinib demonstrated superiority over crizotinib with significant anti-tumor activity, particularly among patients with brain metastases at baseline, after more than 2 years of follow-up.

“Results from the ALTA 1L trial add brigatinib to the very short list of first-line treatment options for ALK-positive [patients with] lung cancer that have proven to be superior to crizotinib. Compared to crizotinib, brigatinib demonstrated superior efficacy, especially among those with brain metastases at baseline, and a low pill burden, at one pill a day, which is an important factor when we could be controlling disease for years,” said Ross Camidge, MD, PhD, Joyce Zeff Chair in Lung Cancer Research, University of Colorado Cancer Center, in a statement. “These data have established brigatinib’s potential in the first-line setting, and I’m confident the FDA approval will open a new window of possibilities for physicians and their patients.”

The objective response rate (ORR) for brigatinib was 74% (95% CI, 66%-81%) compared with an ORR of 62% with crizotinib (95% CI, 53%-70%). The agent also induced a confirmed ORR of 78% in patients with measurable brain metastases at baseline (95% CI, 52%-94%) compared with 26% in the control arm (95% CI, 10%-48%).

Brigatinib reduced the risk of disease progression or death by 51% over crizotinib with a hazard ratio for progression-free survival (PFS) of 0.49. The median PFS was 24 months with brigatinib versus 11 months with crizotinib.

Serious reactions were observed in 33% of the patients who received brigatinib. The most common serious adverse events (AEs) were pneumonia (4.4%), interstitial lung disease/pneumonitis (3.7%), pyrexia (2.9%), dyspnea (2.2%), pulmonary embolism (2.2%), and asthenia (2.2%). Besides disease progression, fatal AEs were observed 2.9% of patients, which included pneumonia (1.5%), cerebrovascular accident (0.7%), and multiple organ dysfunction syndrome (0.7%).

The most common AEs observed in the study included diarrhea (53%), rash (40%), cough (35%), hypertension (32%), fatigue (32%), nausea (30%), myalgia (28%), dyspnea (25%), abdominal pain (24%), and headache (22%).

The international, open-label, comparative, multicenter ALTA-1L study randomized 275 patients 1:1 to receive either 180 mg of brigatinib once daily with a 7-day lead-in period at 90 mg (n = 137) or 250 mg of crizotinib twice daily (n = 138). Crossover to the brigatinib arm was allowed at BICR-assessed PFS.

The median age of patients was 58 years in the brigatinib arm versus 60 years in the crizotinib arm. Approximately 29% of patients had brain metastases at baseline in the brigatinib arm versus 30% in the control, and 26% had prior chemotherapy for advanced or metastatic disease versus 27%, respectively. The primary end point of the trial was PFS, and secondary end points included confirmed ORR and intracranial ORR.

Brigatinib is currently approved in over 40 countries for the treatment of patients with ALK-positive metastatic NSCLC who had received prior crizotinib but had their disease worsen or could not tolerate crizotinib, which include the United States, Canada, and the European Union. The agent is also approved as a monotherapy for the treatment of adult patients with ALK-positive advanced NCLC who had been treated with a previous ALK inhibitor in the European Union.

“We’re extremely proud of the positive results Alunbrig has shown for newly diagnosed ALK-positive [patients with] NSCLC, particularly those with brain metastases,” stated Teresa Bitetti, president, Global Oncology Business Unit, Takeda, in a statement. “Through a robust clinical development program and ongoing investigations across the NSCLC treatment landscape, Takeda is committed to uncovering solutions for people living with devastating forms of lung cancer in need of new options. We believe this approval for Alunbrig is a substantial step in the right direction and represents significant progress for Takeda’s broader lung cancer portfolio.”


US FDA Approves Takeda’s ALUNBRIG® (brigatinib) as a First-Line Treatment Option for Patients Diagnosed with Rare and Serious Form of Lung Cancer [news release]. Cambridge, MA: Takeda Pharmaceutical Company Limited; May 22, 2020. https://bit.ly/2WXl3Iq. Accessed May 22, 2020.